SCN Portal v1.1 (last updated 1st July 2024)

Welcome to the interactive website for families, clinicians, and researchers dedicated to comprehending SCN-related disorders

Individuals
Functionally tested variants
Phenotypes

Latest news for the community

  • Access the latest SCN1A related publications here.
  • Access the latest SCN2A related publications here.
  • Access the latest SCN3A related publications here.
  • Access the latest SCN8A related publications here.

Interested in other Genes?

Visit also our other Gene Portals!

What is new in version 1.1?

  • The general appearance was updated.
  • Variant analysis shows an ACMG criteria-based variant classification.
  • Variant analysis now allows ACMG criteria customization.
  • A report can now be downloaded in the Variant analysis tab.

History of SCN1A research

Discovery of the action potential.
Hodgkin et al.
First description of Dravet Syndrome
Dravet
Defining genetic epilepsy with febrile seizures plus (GEFS+)
Scheffer et al.
Seizure worsening due to sodium channel blockers in Dravet syndrome
Guerrini et al.
First association of SCN1A with GEFS+
Escayg et al.
Stiripentol treatment for Dravet syndrome
Chiron et al.
De novo mutations in SCN1A cause Dravet syndrome
Claes et al.
Selective loss of GABAergic interneurons results in hyperexcitability of pyramidal neurons, leading to seizures in SCN1A mice
Yu et al.
The misconception of vaccine encephalopathy associated with Dravet syndrome
Berkovic et al.
Genotype phenotype associations in large SCN1A cohorts

Harkin et al.
Depienne et al.
Brunklaus et al.
Ishii et al.

First image of the crystal structure of a voltage-gated sodium channel
Payandeh et al.
Autistic-like behaviour in Scn1a+/- mice and rescue by enhanced GABA-mediated neurotransmission
Han et al.
Dravet iPSC-derived neuron work
Liu et al.
Cannabidiol treatment for Dravet syndrome
Devinsky et al.
Fenfluramine treatment for Dravet syndrome
Lagae et al.
Antisense oligonucleotide treatment in Dravet mouse model
Han et al.

SCN1-related disorders

SCN1A , encoding the alpha 1 subunit of the voltage-gated sodium channel Nav1.1, is associated with a wide clinical spectrum of epilepsies ranging from genetic epilepsy with febrile seizures plus (GEFS+), to developmental and epileptic encephalopathies (DEEs). Dravet syndrome (DS) is the prototypic DEE presenting with recurrent, often prolonged febrile and afebrile seizures, including hemiclonic, generalized tonic-clonic seizures and status epilepticus. Subsequently other seizure types, such as myoclonic and atypical absence seizures, emerge as well as long-term problems with learning, motor development and behaviour. In contrast, individuals with GEFS+ phenotypes have well controlled epilepsy with normal cognition. Apart from epilepsy, SCN1A has also been associated with familial hemiplegic migraine, a subtype of migraine with aura characterised by hemiparesis during the attacks.

Tretament options

For more information on possible treatment options, please visit the appropriate family organization website: Family organisations

Clinical information from the SCN registry

DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development

DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development

DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development

DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development

DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development

DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development

History of SCN2A research

Discovery of SCN2A
Litt et al.
SCN2A related benign familial epilepsy
Berkovic et al.
SCN2A as a cause for autism
Sanders et al.
Correlations between functional outcome and phenotype
Wolff et al.
Current knowledge on SCN2A-related disorders
Sanders et al.
SCN2A and episodic ataxia
Schwarz et al.

SCN2A-related disorders

SCN2A -related disorders are characterized by a wide clinical spectrum ranging from benign familial infantile seizures to developemental and epileptic encephalopathy. Furthermore, SCN2A is one of the most prominent monogenic causes of autism spectrum disorders. Variants causing both gain and loss of function have been identified as the underlying pathomechanism. Correlations between functional outcome and clinical phenotype includes: autism and/or late onset epilepsy for individuals with loss of function variants and neonatal onset self-limiting epilepsy or neonatal/infantile DEE with gain of function variant. As subset of individuals with self-limiting epilepsy develop episodic ataxia later in childhood.

Tretament options

For more information on possible treatment options, please visit the appropriate family organization website: Family organisations

Clinical information from the SCN registry

DEE: Developmental epileptic encephalopathy

DEE: Developmental epileptic encephalopathy

DEE: Developmental epileptic encephalopathy

DEE: Developmental epileptic encephalopathy

DEE: Developmental epileptic encephalopathy

History of SCN3A research

First association of SCN3A and epilepsy
Holland et al.
Delineation of the phenotype
Zamam et al.

SCN3A-related disorders

SCN3A -related disorders are characterized mainly by epilepsy often associated with brain malformations such as polymicrogyria (abnormal gyration of the brain). Affected individuals often have intellectual disability. Seizure types varies, and includes focal, febrile, myoclonic and tonic seizures among others. Functional studies have revealed both gain and loss of function as underlying pathomechanism. Because of a small number of known affected individuals, correlations between functional outcome, genotype and phenotype are still sparse. The limited data there is, suggests that brain malformations are mainly seen in individuals with gain of function variants, while epilepsy and intellectual disability are seen in both individuals with gain and loss of function variants.

Tretament options

For more information on possible treatment options, please visit the appropriate family organization website: Family organisations

Clinical information from the SCN registry

GEFS +: Generalized epilepsy with febrile seizures plus; DEE: Developmental and Epileptic Encephalopathies; PMG: Polymicrogyria; ASD: Autism spectrum disorder

GEFS +: Generalized epilepsy with febrile seizures plus; DEE: Developmental and Epileptic Encephalopathies; PMG: Polymicrogyria; ASD: Autism spectrum disorder

History of SCN8A research

Discovery of SCN8A
Burgess et al.
First epilepsy patient described
Veeramah et al.
Further characterization of the phenotype
Ohba et al.
First SCN8A DEE mouse model
Wagnon et al.
Delineation of the phenotype
Larsen et al.
Sodium channel blocker treatment for SCN8A DEE
Boerma et al.
Description of SCN8A in BFIE
Gardella et al.
First description of individuals with LOF missense variants
Wagnon et al.
Neuronal hyperexcitability in a mouse model of SCN8A epileptic encephalopathy
Lopez-Santiago et al.
The phenotype of SCN8A DEE
Gardella et al.
Prominent role of forebrain excitatory neurons in SCN8A encephalopathy
Bunton-Stasyshyn et al.
Antisense oligonucleotide treatment in SCN8A mouse model
Lenk et al.
Correlation between functional outcome and phenotype
Johannesen et al.

SCN8A-related disorders

SCN8A, encoding the alpha subunit of the voltage-gated sodium channel Nav1.6, is associated with a wide clinical spectrum of epilepsies ranging from benign familial infantile seizures (BFIS), over an intermediate phenotype with treatable seizures and mild-moderate intellectual disability, to severe developmental and epileptic encephalopathies (DEEs). SCN8A-DEE is characterized by early onset intractable seizures, cognitive impairment, movement disorders, cortical visual impairment and severe gastrointestinal symptoms. The seizures are often prolonged focal hypomotor and occur in clusters, with prominent vegetative symptoms, evolving to clonic or bilateral tonic-clonic manifestations. Spasm-like episodes, cortical myoclonus, and recurrent episodes of status epilepticus are also common. In contrast, individuals with BFIS have well controlled self-limiting epilepsy with no other neurological deficits and normal cognition. In addition, rare clinical presentations with ID, autism spectrum disorder and movement disorders without epilepsy have been described.

Tretament options

For more information on possible treatment options, please visit the appropriate family organization website: Family organisations

Clinical information from the SCN registry

DEE: Developmental and Epileptic Encephalopathies; BFIE: Benign Familial Infantile Epilepsy; GGE: Genetic Generalized Epilepsy; IE: Intermediate Epilepsy; UE: Unclassifiable Epilepsy; NDDwoe: Neurodevelopmental Disorder without Epilepsy

DEE: Developmental and Epileptic Encephalopathies; BFIE: Benign Familial Infantile Epilepsy; GGE: Genetic Generalized Epilepsy; IE: Intermediate Epilepsy; UE: Unclassifiable Epilepsy; NDDwoe: Neurodevelopmental Disorder without Epilepsy

DEE: Developmental and Epileptic Encephalopathies; BFIE: Benign Familial Infantile Epilepsy; GGE: Genetic Generalized Epilepsy; IE: Intermediate Epilepsy; UE: Unclassifiable Epilepsy; NDDwoe: Neurodevelopmental Disorder without Epilepsy

What are SCN-related disorders?

Expert curated subtitles available in English, German, Danish, Greek, Russian, Spanish, Italian, Ukrainian, and Romanian.


SCN1A

Expert curated subtitles available in English, German, Danish, Greek, Russian, Spanish, Italian, Ukrainian, and Romanian.

SCN2A

Expert curated subtitles available in English, German, Danish, Greek, Russian, Spanish, Italian, Ukrainian, and Romanian.

If your family has received a diagnosis of an SCN-related neurodevelopmental disorder, you've probably never heard of it before. That's okay. Your doctors probably haven't either! But the Educational Science community is here to help.

In this section, you can find a series of short explainer videos that are designed to help patients, families, and clinicians to learn about SCN-related neurodevelopmental disorders in plain language. Over time, we'll be adding more content to cover all SCN genes and related topics.

The series starts with an overview video about all SCN-genes included in this Portal:SCN1A, SCN2A, SCN3A, SCN8A.

Next, we present a comprehensive video on SCN1A-related disorders and introductory video on SCN2A-related disorders.

From this videos you'll learn:

  • Scientific terms (such as genes, proteins and variants/mutations) that will help you understand SCN-related disorders
  • What causes SCN-related disorders
  • How SCN-related disorders are diagnosed
  • The symptoms of SCN-related disorders
  • Existing options for symptom treatment, as there is currently no cure for SCN-related disorders
  • Where to find support

























...and many more! Please contact us if you would like your organization to be listed here.

How to analyse your variant

Discover how to customize variant classifications by exploring our tutorial.
Filtered Subset

Variant location


Transcripts: SCN1A: NM_001165963.4, SCN2A: NM_001040142.2, SCN3A: NM_006922.4, SCN8A: NM_001330260.2


UniProt SCN1A: P35498
Variants mapped on the protein structure of Nav.1.1 using PDB: 7DTD
UniProt SCN2A: Q99250
Variants mapped on the protein structure of Nav.1.2 using PDB: 6J8E


UniProt SCN3A: Q9NY46
Variants mapped on the protein structure of Nav.1.2 (via protein sequence alignment) using PDB: 6J8E


UniProt SCN8A: Variants mapped on the protein structure of Nav.1.2 (via protein sequence alignment) using PDB:
O88420 6J8E
Filtered Subset

Phenotype interface

Abbreviations: DEE: Developmental epileptic encephalopathy; MD: Movement disorder; DEEMA: Developmental and Epileptic Encephalopathy with Malformations of Cortical Development; GEFS +: Generalized epilepsy with febrile seizures plus; PMG: Polymicrogyria; ASD: Autism spectrum disorder; BFIE: Benign Familial Infantile Epilepsy; GGE: Genetic Generalized Epilepsy; IE: Intermediate Epilepsy; UE: Unclassifiable Epilepsy; NDDwoe: Neurodevelopmental Disorder without Epilepsy
Filtered Subset

Functional interface

All functional measures are displayed on the Nav1.2 structure: 6J8E

Portal version 1.1

The SCN Portal is a coalition of investigators seeking to aggregate and harmonize data generated to study SCN-related disorders, and to make summary data interactively accessible for the wider scientific community, while providing educational resources for everyone. The goals of this project are:

  • Providing information on SCN-related disorders

  • Supporting research on SCN-related disorders

  • Facilitating recruitment of individuals to the global SCN registries

  • Providing support in variant interpretation and classification

  • Visualizing data from the global SCN registries

  • Linking researchers, clinicians and families


The SCN Portal is an ongoing project and interested collaborators are invited to reach out to join the project. The current version of the SCN Portal has been developed by an international team of researchers and clinicians:

Team Leaders

Andreas Brunklaus (Glasgow, UK): SCN1A Clinical & genetic data

Stephanie Schorge (London, UK): Functional data curation

Rikke Møller (Dianalund, DK): SCN1A , SCN2A , SCN8A Clinical & genetic data

Ingo Helbig (Philadelphia, US): SCN2A Clinical & genetic data

Jen Q Pen (Cambride, US): SCN2A High-throughput functional data

Alfred George (Chicago, US): SCN1A & SCN2A High-throughput functional data

Dennis Lal (Cleveland, US): General concept, web development, bioinformatics, video production

Clinical & Genetic Data

Katrine Johannesen

Ingo Helbig

Sameer Zuberi

Molecular Data

Holger Lerche

Massimo Mantegazza

Sandrine Cestele

Web Development

Tobias Brünger

Arthur Stefanski

Chiara Klöckner

Marie Mcnee

Tobias Brünger

Eduardo Perez-Palma

Bioinformatics

Chiara Klöckner

Tobias Brünger

Eduardo Perez-Palma

Marie Mcnee

Patrick May

Video

Arthur Stefanski

Alina Ivaniuk

Andreas Brunklaus

Katrine Johannesen

Family outreach

Mary Anne Meskis : SCN1A

Veronica Hood : SCN1A

Leah Schust : SCN2A

Impressum

We object to any commercial use and disclosure of data.

Copyright and use: The authors grants you the right of use to make a private copy for personal purposes. However, you are not entitled to change and/or pass on the materials or publish them yourself. Upon request, you will receive free information about the personal data stored about you. To do so, please contact the administrator.

No liability: The contents of this web project have been carefully checked and created to the best of our knowledge. But for the information presented here is no claim to completeness, timeliness, quality and accuracy. No responsibility can be accepted for any damage caused by reliance on or use of the contents of this website.

Terms of Use

All data here are publicly for the benefit of the wider biomedical community. You can freely explore the data, and we encourage the use and publication of results generated from these data. However, we encourage you to contact us before embarking on analyses to check if your proposed analysis overlaps with our team's current work. Further, we request that you actively acknowledge and give attribution to the SCN Portal project and link back to the relevant page, wherever possible. All users of our data agree not to attempt to reidentify participants. Our data set has been subjected to extensive quality control but may be imperfect so that errors may remain.
If you spot any results that seem impossible or have suggestions for SCN Portal improvements: contact us so that we can improve.

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